title: BRCA1-Dependent Translational Regulation in Breast Cancer Cells.
abstract: BRCA1 (Breast Cancer 1) has been implicated in a number of cellular processes, including transcription regulation, DNA damage repair and protein ubiquitination. We previously demonstrated that BRCA1 interacts with PABP1 (Poly(A)-Binding Protein 1) and that BRCA1 modulates protein synthesis through this interaction. To identify the mRNAs that are translationally regulated by BRCA1, we used a microarray analysis of polysome-bound mRNAs in BRCA1-depleted and non-depleted MCF7 cells. Our findings show that BRCA1 modifies the translational efficiency of approximately 7% of the mRNAs expressed in these cells. Further analysis revealed that several processes contributing to cell surveillance such as cell cycle arrest, cell death, cellular growth and proliferation, DNA repair and gene expression, are largely enriched for the mRNAs whose translation is impacted by BRCA1. The BRCA1-dependent translation of these species of mRNAs therefore uncovers a novel mechanism through which BRCA1 exerts its onco-suppressive role. In addition, the BRCA1-dependent translation of mRNAs participating in unexpected functions such as cellular movement, nucleic acid metabolism or protein trafficking is indicative of novel functions for BRCA1. Finally, this study contributes to the identification of several markers associated with BRCA1 deficiency and to the discovery of new potential anti-neoplastic therapeutic targets.
authors.affiliation: Université de Lyon, Lyon, France ; Université Lyon 1, ISPB, Lyon, France ; INSERM U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France ; CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France ; Equipe Labellisée LIGUE 2008, Lyon, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Dacheux
authors.forename: Anne
authors.initials: A
authors.lastname: Vincent
authors.forename: Nicolas
authors.initials: N
authors.lastname: Nazaret
authors.forename: Christophe
authors.initials: C
authors.lastname: Combet
authors.forename: Anne
authors.initials: A
authors.lastname: Wierinckx
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mazoyer
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Diaz
authors.forename: Joël
authors.initials: J
authors.lastname: Lachuer
authors.forename: Nicole Dalla
authors.initials: ND
authors.lastname: Venezia
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D039122:Poly(A)-Binding Protein I / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor; D039122:Poly(A)-Binding Protein I; D012333:RNA, Messenger; D012334:RNA, Neoplasm